Background: Docetaxel and cabazitaxel represent now the standard of care in men with mCRPC with similar efficacy reported in metastatic first-line setting in the FIRSTANA phase 3 trial. We assessed patients’ preference between the two taxanes. Methods: Patients with taxane-naïve mCRPC were randomized in a 1:1 ratio to receive either docetaxel 75mg/m2/q3w x 4 followed by cabazitaxel 25mg/m2/q3w x 4 (DO-CA), or the reverse sequence (CA-DO). Randomization was stratified based on prior next generation AR axis inhibitors use. The primary endpoint was patient preference between taxanes, as assessed by questionnaires in patients who had received at least one cycle of each taxane and who had not experienced a progression while on the first taxane. Results: From June 2014 to October 2016, 195 men were randomized in 17 centers. After adjusting for the treatment period effect, more patients preferred cabazitaxel (43%) vs docetaxel (27%) (p < 0.004); 30% had no preference between taxanes. Fatigue, patient-defined quality of life, hair loss, and pain were the most common factors influencing patient preference. Febrile neutropenia was experienced by 5 (7.1%) men treated with cabazitaxel during the first period who received G-CSF and by 2 (7.1%) of those who did not. No febrile neutropenia was reported with docetaxel in both arms and with cabazitaxel during the 2nd period, irrespectively of the use of G-CSF. The incidence of diarrhea during the first 3-month period was slightly reduced with G-CSF use in men receiving cabazitaxel (32.1% vs 24.3%) but not in those receiving docetaxel (23.8% vs 25%). The median progression-free survival was 9.81 in the DO-CA arm and 9.33 months in the CA-DO arm. The median overall survival was also similar in the two groups (22.64 in the DO-CA arm and 20.73 months in the CA-DO arm. Conclusions: Although cabazitaxel and docetaxel have similar efficacy when used as first-line in mCRPC men, more patients prefer cabazitaxel. Clinical trial information: NCT02044354